Source: Myeloma – Hematology Advisor

The splicing factor protein serine/arginine repetitive matrix 2 (SRRM2) may serve as a novel biomarker and immunotherapeutic target in multiple myeloma (MM), according to research published in Clinical and Experimental Medicine.

“New drugs and immunotherapy bring new changes to the prognosis of MM and need to be supplemented with more diagnostic, risk stratification, and prognostic markers for clinical application,” the authors wrote in their report. “There are data sets showing that increased expression of SRRM2 is associated with poor survival in acute myeloid leukemia, renal, and hepatocellular carcinoma.”

The researchers investigated whether SRRM2 could serve as a potential biomarker and immunotherapeutic target in MM by comparing its expression on plasma cells and normal blood cells using flow cytometry. The team also evaluated its correlation with other clinical data and treatment response.

The study included 102 bone marrow or peripheral blood samples from 95 patients with plasma cell disease, including 80 patients with MM. The analysis revealed SRRM2 expression on plasma cells was significantly higher than that on normal blood cells in all subgroups analyzed, and its expression on aberrant plasma cells was higher than that on normal plasma cells. 

We demonstrated that SRRM2 is a novel biomarker for MM and has the potential to serve as a target for immunotherapy in this disease.

SRRM2 expression on plasma cells was correlated with MM treatment response. In patients with newly diagnosed MM, those with high SRRM2 expression (vs SRRM2-negative) had higher levels of serum β2-microglobulin and lactate dehydrogenase, International Staging System stage, and plasma cell infiltration, as well a high-risk mSMART 3.0 stratification and more cytogenetic abnormalities.

Similar results were observed in patients with previous MM. Those with high SRRM2 expression on plasma cells had higher plasma cell infiltration, high-risk mSMART 3.0 risk stratification, more cytogenetic abnormalities, more relapses, and fewer autologous stem cell transplant treatments. 

“In summary, we demonstrated that SRRM2 is a novel biomarker for MM and has the potential to serve as a target for immunotherapy in this disease,” the authors concluded. “The expression level of SRRM2 on plasma cells can aid in risk stratification and monitoring of treatment responses in MM.”

The investigators noted that no significant differences were observed in the expression of some inflammatory and iron metabolism-related markers associated with prognosis in MM between the SRRM2-negative and SRRM2-positive groups, potentially limiting the prognostic relevance of SRRM2 in MM.

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